TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31050	93373;93374;93375	chr2:178548478;178548477;178548476	chr2:179413205;179413204;179413203
N2AB	29409	88450;88451;88452	chr2:178548478;178548477;178548476	chr2:179413205;179413204;179413203
N2A	28482	85669;85670;85671	chr2:178548478;178548477;178548476	chr2:179413205;179413204;179413203
N2B	21985	66178;66179;66180	chr2:178548478;178548477;178548476	chr2:179413205;179413204;179413203
Novex-1	22110	66553;66554;66555	chr2:178548478;178548477;178548476	chr2:179413205;179413204;179413203
Novex-2	22177	66754;66755;66756	chr2:178548478;178548477;178548476	chr2:179413205;179413204;179413203
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-114
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.2843
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
H/R	None	None	1.0	N	0.669	0.486	0.313210971179	gnomAD-4.0.0	3.18226E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71611E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
H/A	0.4814	ambiguous	0.4732	ambiguous	-0.951	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
H/C	0.2441	likely_benign	0.2578	benign	-0.023	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
H/D	0.3392	likely_benign	0.2865	benign	-0.779	Destabilizing	1.0	D	0.745	deleterious	N	0.464999229	None	None	I
H/E	0.5518	ambiguous	0.5242	ambiguous	-0.651	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	I
H/F	0.4626	ambiguous	0.4735	ambiguous	0.509	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
H/G	0.3115	likely_benign	0.2738	benign	-1.341	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
H/I	0.8171	likely_pathogenic	0.8149	pathogenic	0.152	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
H/K	0.6255	likely_pathogenic	0.5863	pathogenic	-0.592	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
H/L	0.3979	ambiguous	0.3803	ambiguous	0.152	Stabilizing	1.0	D	0.786	deleterious	N	0.490207055	None	None	I
H/M	0.7585	likely_pathogenic	0.7667	pathogenic	0.027	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
H/N	0.1073	likely_benign	0.1009	benign	-0.774	Destabilizing	0.999	D	0.507	neutral	N	0.396459242	None	None	I
H/P	0.947	likely_pathogenic	0.9192	pathogenic	-0.198	Destabilizing	1.0	D	0.811	deleterious	N	0.508653705	None	None	I
H/Q	0.3398	likely_benign	0.3378	benign	-0.46	Destabilizing	1.0	D	0.695	prob.neutral	N	0.471342331	None	None	I
H/R	0.2978	likely_benign	0.2701	benign	-1.094	Destabilizing	1.0	D	0.669	neutral	N	0.515246496	None	None	I
H/S	0.2301	likely_benign	0.2205	benign	-0.8	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
H/T	0.4435	ambiguous	0.4463	ambiguous	-0.57	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
H/V	0.7291	likely_pathogenic	0.7228	pathogenic	-0.198	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
H/W	0.65	likely_pathogenic	0.6156	pathogenic	0.818	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
H/Y	0.1361	likely_benign	0.1331	benign	0.847	Stabilizing	0.999	D	0.539	neutral	N	0.506589727	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.